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bioRxiv · 10.1101/2023.12.21.572681

Chromatin Remodeling and Epigenetic Modifications in Planar Cell Migration

Forman, J.·Hine, B.·Kaonis, S.·Ghosh, S.
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Abstract

The cell nucleus plays a critical role in cell migration by its deformability under forces, by acting as a piston that activates mechanosensitive channels, and also by serving as a ruler tailoring cell response to spatial constraints. Cell nuclear mechanics determine the mechanobiology of static and migrating cells. Here, we report that intranuclear chromatin architecture plays a previously unknown role during cell migration on planar substrates. By inhibiting histone deacetylation, which compacts chromatin, and a methyltransferase, which affects chromatin remodeling and chromatin compaction, we showed that cell migration speed and persistence drastically slowed wound closure efficiency in an in vitro scratch wound assay. Chromatin remodeling was visualized and quantified during cell migration, which may be intertwined with nuclear mechanics and shape. Inhibition disrupts remodeling and other unknown roles in chromatin, thus affecting the speed and persistence of cell migration. Interestingly, cytoskeletal stress fiber formation and cell shape were not visibly affected by chromatin modifications, suggesting an exclusive nuclear mechanobiological role in cell migration. These findings provide new insights into how aging and other degenerative conditions affect the plasticity of chromatin architecture and hence its effect on cell migration efficiency.

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Forman, J., Hine, B., Kaonis, S., Ghosh, S.. 2023-12-22. Chromatin Remodeling and Epigenetic Modifications in Planar Cell Migration. https://doi.org/10.1101/2023.12.21.572681

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